FSMP-05. KETOGENIC DIETS FOR HIGH-GRADE GLIOMA

BACKGROUND: Given therapeutic challenges posed by high-grade glioma (HGG), multiple concomitant therapies, including metabolic adjuncts to standard of care, are warranted. Tumor cells are almost exclusively energy-dependent on glucose. Preclinical data supports the use of ketogenic diets (KDs) in this population to deplete the tumor microenvironment of glucose, thereby exerting anti-tumor effects while the surrounding parenchymal tissue utilizes ketones. OBJECTIVE: The aim of this study was to conduct an up-to-date systematic review of the clinical use of ketogenic diets (KD) in the setting of high-grade glioma treatment and compare study designs, outcomes, and challenges in the translation of these methods from bench to bedside. METHODS: We conducted comprehensive searches of both the national clinical trials database (clinicaltrials.gov) and pubmed.gov. Trials were included in our review if they were conducted in a patient population with high-grade glioma (either early or refractory) and at least one study arm included the use of a KD. RESULTS: The clinicaltrials.gov search yielded 12 studies of which 11 met inclusion criteria. Five of these trials reported results. The PubMed search yielded 2 additional studies. Seven clinical trials with reported results on a total of 69 patients were considered. CONCLUSIONS: The use of KD has proven to be safe and tolerable in early trials, however, further studies are warranted to examine efficacy. Challenges to feasibility include low patient enrollment and compliance, as dietary changes were reported to negatively affect quality of life. Additionally, variability between animal and plant-based KDs, duration of KD regimen, carbohydrate: fat ratio, underlying genetic factors that affect the induction of ketosis, and use of steroid therapy in this patient population may all contribute to inconsistent clinical data when compared to preclinical studies. Future larger scale clinical trials and prospective studies are needed to clarify the role of KDs in the treatment of HGG.